My immediate goals are to establish myself as an independent researcher, to gain an understanding for the interaction of methamphetamine (MA) and the hypothalamic-pituitary-adrenal (HPA) axis during development, and to increase my experience in methods related to learning and memory. For my long-term goals, I see myself in an academic position that allows for interaction among a variety of fields and interests with the possibility of collaborative work. I would like to be in a position to be promoted to a tenure track position and to gain tenure. My research pursuits will continue to be in the areas of drugs of abuse, development, learning and memory, neurotrophic factors, gene expression, and hormones. I feel that concurrent investigation of these areas will provide possible mechanisms for the development of cognitive deficits following drug exposure. Since very little research has incorporated all of these areas in a focused manner, this research will enable me to have a strong influence in developmental problems associated with early drug exposure, especially MA. MA use has reached epidemic proportions in a very short period of time. Very few data exist for the effects of MA during development in humans, therefore of particular concern is that women of childbearing age are among the growing number of users/abusers. Research in Dr. Charles V. Vorhees' laboratory, the mentor for the proposed application, has demonstrated that rats exposed to MA during a period of hippocampal development that correlates with third trimester human development, show cognitive impairments as adults, without apparent alterations to neurotransmitters or neurotoxicity during drug administration. Recently we have demonstrated that MA administration on P11-20 causes elevated corticosterone (CORT) and ACTH levels. The proposed studies will investigate the interaction of MA and the hormones of the HPA axis to determine if the elevation in these hormones mediates the cognitive deficits. Several converging lines of research will be used to determine these effects. Investigations will include assessing the dose-dependent response of the HPA axis to MA, the critical period of hormone release, the effect early MA exposure has on the development of the HPA axis and release of these hormones following exposure to an environmental challenge (either forced swim in a novel environment, or a novel environment alone). Further, experiments investigating the effect of CORT on cell proliferation, development, and receptors has been proposed. Investigation of gene expression changes will be undertaken. The use of different strains of rats prone to hyper- or hyposecretion of HPA axis hormones will be used, as will animals that are exposed to MA without the concurrent increase in CORT.